1. Field of the Invention
The invention generally relates to the field of orthopaedic implants. Specifically the prevention and decrease of osteolysis produced by wear of ultrahigh molecular weight polyethylene (UHMWPE) bearing components. Methods are disclosed for the isolation of wear particles, preparation of implants having decreased wear and preparation of implants causing decreased biological response. The implants created by these methods are also included in the present invention.
2. Related Art
Ultrahigh molecular weight polyethylene (UHMWPE) is commonly used as an articulating, load-bearing surface in total joint arthoplasty due to its unique array of properties. UHMWPE offers toughness, low friction coefficient, and biocompatibility. (Baker et al., 1999) Total joint prosthesis, composed of various combinations of metal, ceramic, and polymeric components, suffer from limited service lives and wear of UHMWPE is the limiting factor. It has become apparent that wear debris from UHMWPE components may be a primary contributor to osteolysis, loosening and eventual revision surgery. With steady increases in human life expectancy, there is a driving need to significantly increase the effective lifetime of a single implant. A desire to use prosthetic implants in younger patients is another strong incentive for improving the wear resistance of UHMWPE. The present invention discloses a process to improve long term wear characteristics of prosthetic implants made with UHMWPE.
When a human joint is destroyed or damaged by disease or injury, surgical replacement (arthoplasty) is normally required. A total joint replacement includes components that simulate a natural human joint, typically:
(a) a more-or-less spherical ceramic or metal ball, often made of cobalt chromium alloy;
(b) attachment of a xe2x80x9cstemxe2x80x9d, which is generally implanted into the core of the adjacent long bone; and
(c) a hemispherical socket which takes the place of the acetabular cup and retains the spherical ball.
This hemispherical joint typically is a metal cup affixed into the joint socket by mechanical attachments and is lined with UHMWPE. In this way, the ball can rotate, pivot, and articulate within the socket, and the stem, via the ball, can pivot and articulate.
One of the difficulties in constructing any device for implantation into the human body is the need to avoid adverse host biological responses. The probability of adverse host reaction is reduced when certain synthetic materials are used. For example, synthetic UHMWPE implants have minimal immunogenicity and are not toxic. However, the wear and breakdown of the UHMWPE components are known in the art to cause host cellular responses, which ultimately lead to revision surgery.
Histologic studies have demonstrated that wear of UHMWPE from orthopaedic inserts leads to several reactions. First, the tissue surrounding implants that were constructed with UHMWPE has been shown to contain extremely small particles of UHMWPE that range from sub-micron to a few microns in size. While large particles of UHMWPE appear to be tolerated by the body, as is the intact solid wall of the UHMWPE implant, the body apparently does not tolerate smaller particles of UHMWPE. In fact, the small particles of UHMWPE can cause histiocytic reactions by which the body attempts to eliminate the foreign material. Agents released during this process cause wear debris induced osteolysis. This in turn can lead to loss of fixation and loosening of the prosthesis.
Numerous techniques have been proposed to improve wear resistance of UHMWPE in orthopaedic implants. In these instances, however, many of the new versions of articulating polymers have generally failed to demonstrate significant reduction in wear and often prove to be inferior to conventional polyethylene. Recent attempts at improving wear properties of UHMWPE use special pressure/temperature processing techniques, surface treatments, formation of composites with high modulus fibers, and cross-linking via ionizing irradiation or chemical agents. Some of these attempts are summarized below.
Special thermal and pressure treatments have been used to increase physical performance and wear resistance of UHMWPE (e.g., U.S. Pat. Nos. 5,037,928 and 5,037,938). For example, xe2x80x9cHippingxe2x80x9d (Hot Isostatic Pressing), produces material alleged to comprise fewer fusion defects, increased crystallinity, density, stiffness, hardness, yield strength and resistance to creep, oxidation, and fatigue. Clinical studies, however, indicate that xe2x80x9cHippingxe2x80x9d treated UHMWPE may possess inferior wear resistance in comparison to conventional UHMWPE. The inferior wear resistance being due to increased stiffness which leads to increased contact stresses during articulation (Livingston et al., Trans. ORS, 22, 141-24, 1997).
Post-consolidation temperature and pressure treatment, such as solid phase compression molding (Zachariades, U.S. Pat. No. 5,030,402), have also been attempted. Zachariades utilized solid state processing to further consolidate and orient UHMWPE chains. Resistance to wear in orthopaedic implants, however, was not improved.
Focusing upon the surface of UHMWPE components, attempts have been made to decrease wear by increasing smoothness and/or lubricity of the UHMWPE components surface. A group from Howmedica used a heat pressing technique to melt the articulating surface and remove machine marks from the surface of UHMWPE components such that the xe2x80x9cwearing inxe2x80x9d of rough machine marks could be avoided. This modification, however, resulted in delamination and high wear due to the fact that high articulationxe2x80x94induced stresses were located in regions where there was a sharp transition in crystalline morphology (Bloebaum et al., Clin. Orthop. 269, 120-127, 1991).
Andrade et al. (U.S. Pat. No. 4,508,606) suggested oxidizing the surface of a wet hydrophobic polymer surface to reduce sliding friction. The preferred means included applying a radio frequency glow discharge to the surface. With this technique, surface chemistries were altered by changing the time of gas plasma exposure and by altering the gas composition. The invention was proposed for the treatment of catheters to decrease surface friction properties while in a wet state. Similarly, Farrar (World Patent Application No. WO 95 212212) proposed using gas plasma treatments to cross-link the surface of UHMWPE and, thereby, increase its wear resistance. None of the plasma treatments, however, were practical because any perceived benefit would most likely wear away with articulation.
Because creep may be a contributor to UHMWPE wear, investigators have also included high modulus fibers in polyethylene matrices to reduce plastic deformation. (U.S. Pat. No. 4,055,862 discloses a xe2x80x9cpoly-to-carbon polyethylene compositexe2x80x9d which failed significantly via delamination. Recently, Howmedica reported that a PET/carbon fiber composite exhibited 99% less hip simulated wear than conventional polyethylene over ten million cycles. (Polineni, V. K. et al., J. 44th Annual ORS, 49, 1998.)
Radiation Induced Cross-Linking
In the absence of oxygen, the predominant effect of ionizing radiation on UHMWPE is cross-linking (Rose et al., 1984, Streicher et al., 1988). Cross-linking of UHMWPE forms covalent bonds between polymer chains which inhibit cold flow (creep) of individual polymer chains. Free radicals formed during irradiation, however, can exist indefinitely if termination by cross-linking or other forms of recombination do not occur. Furthermore, reacted intermediates are continuously formed and decayed. Exposure of these free radical species at any time (e.g., during irradiation, shelf-aging, or in vivo aging) to molecular oxygen or any other reactive oxidizing agent can result in their oxidation. Extensive oxidation leads to a reduction in molecular weight, and subsequent changes in physical properties, including wear resistance.
To reduce oxidation after gamma sterilization, some orthopaedic manufacturers have implemented techniques to irradiate their materials under conditions that encourage cross-linking and reduce oxidation. These techniques include use of inert gas atmospheres during all stages of processing, use of vacuum packaging, and post sterilization thermal treatments. Specific examples of these techniques are given below.
Howmedica has developed various means for reducing UHMWPE oxidation associated with processing, i.e., the continual use of an inert gas during processing (see U.S. Pat. Nos. 5,728,748; 5,650,485; 5,543,471; 5,414,049; and 5,449,745). These patents also describe thermal annealing of the polymer to reduce or eliminate free radicals. The annealing temperature which is claimed (room temperature to 135xc2x0 C.), however, avoids complete melting of UHMWPE.
Johnson and Johnson has disclosed in a European patent application (EP 0737481 A1) a vacuum packaging method with subsequent irradiation sterilization to promote cross-linking and reduce short- and long-term oxidative degradation. The packaging environment can contain an inert gas and/or hydrogen to xe2x80x9cquenchxe2x80x9d free radicals. The cross-linking/sterilization method is claimed to enhance UHMWPE wear resistance (Hamilton, J. V. et al., Scientific Exhibit, 64th AAOS Meeting, February 1997; Hamilton, J. V. et al., Trans 43rd ORS, 782, 1997.).
Biomet""s World Patent Application No. 97/29787 discloses the gamma irradiation of a prosthetic component in an oxygen resistant container partially filled with a gas capable of combining with free radicals (e.g., hydrogen).
Oonishi/Mizuho Medical Company-Japan and other investigators from Mizuho Medical Company began cross-linking PE (polyethylene) by gamma irradiation in 1971 for their SOM hip implants. Since then, they have studied the effect of a wide range of sterilization doses up to 1,000 MegaRad (MRad) on the mechanical, thermal, and wear properties of UHMWPE. They have also studied the effects of different interface materials on wear and found that alumina or zirconia heads on 200 MRad irradiated UHMWPE liners produced the lowest wear rates (Oonishi, H. et al., Radiat. Phys. Chem., 39(6), 495, 1992; Oonishi, H. et al., Mat. Sci: Materials in Medicine, 7, 753-63, 1966; Oonishi, H. et al., J. Mat. Sci: Materials in Medicine, 8, 11-18, 1997).
Massachusetts General Hospital/Massachusetts Institute of Technology (MGH/MIT) has used irradiation (especially e-beam) treatments to cross-link UHMWPE. These treatments reduced simulator wear rates of hip components by 80 to 95% in comparison to non-sterilized controls (see, e.g., World Patent Application 97/29793). This technology enables UHMWPE to be cross-linked to a high degree; however, the degree of cross-linking is dependent upon whether the irradiated UHMWPE is in a solid or molten state. Massachusetts General Hospital/Massachusetts Institute of Technology (MGH/MIT) has also disclosed the crosslinking of UHMWPE at greater than about 1 MRad, preferably greater than about 20 MRad to reduce the production of fine particles (U.S. Pat. No. 5,879,400). They disclosed a wear rate of 8 mg/million cycles for the unirradiated pin and 0.5 mg/million cycles for the irradiated (20MRad) UHMWPE pin.
Orthopaedic Hospital/University of Southern California has disclosed patent applications which seek to increase the wear resistance of UHMWPE hip components using irradiation followed by thermal treatment, such as remelting or annealing (World Patent Application WO 98/01085). Irradiation of the UHMWPE was disclosed at 1-100 MRad, more preferably 5-25 MRad, and most preferably 5-10 MRad. Wear rates were disclosed for various doses of irradiation. Using this method, UHMWPE cross-linking was optimized such that the physical properties were above ASTM limits.
In U.S. Pat. No. 6,165,220, McKellop et al., has disclosed the crosslinking of UHMWPE at 1-25 MRad, more preferably 1-15 MRad, and most preferably 10 MRad. Oxidation profiles were given for UHMWPE crosslinked with 5, 10, or 15 MRad. They did not look at the size or number of wear particles.
BMG""s European Application (EP 0729981 A1) discloses a unique processing method for decreasing friction and abrasive wear of UHMWPE used in artificial joints. The method involves irradiating UHMWPE at a low dose to introduce a small number of cross-linking points. Irradiation is followed by uniaxial compression of melted material to achieve molecular and crystallite orientation. BMG""s material demonstrated a significant reduction in pin-on-disk wear, but the reduction was not as significant as with highly cross-linked versions of UHMWPE (Oka, M. et al., xe2x80x9cWear-resistant properties of newly improved UHMWPE,xe2x80x9d Trans. 5th World Biomaterials Congress, 520, 1996).
In U.S. Pat. No. 6,017,975, Saum et al., has disclosed the crosslinking of UHMWPE at 0.5-10 MRad, and more preferably 1.5-6 MRad to improve wear properties. They determined the wear rate for MRad up to 5 MRad but did not look at the size and number of wear particles.
Yamamoto et al. discloses an analysis of the wear mode and morphology of wear particles from crosslinked ultrahigh molecular weight polyethylene. The ultrahigh molecular weight polyethylene was crosslinked at 0-150 MRad gamma irradiation. Yamamoto et al. stated that the size of both cup surface fibrils and wear debris decrease in proportion to the dose of gamma irradiation. (Yamamoto et al., Trans. 6th World Biomaterials Congress, 485, 2000).
Importantly, for these methods, thermal annealing of the polymer during or after irradiation causes the free radicals (generated during irradiation) to recombine and/or form a more highly cross-linked material. Reducing or quenching free radicals is extremely important because a lack of free radicals can prevent significant UHMWPE aging.
B. Chemical Cross-Linking
Like irradiation cross-linking, chemical cross-linking of UHMWPE has been investigated as a method for increasing wear resistance. Chemical cross-linking provides the benefit of cross-linking while avoiding the degradative effects of ionizing irradiation.
The Orthopaedic Hospital/University of Southern California has submitted patent applications for cross-linking UHMWPE in order to increase wear resistance in orthopaedics (European Patent Application EP 0722973 A1), including a method wherein the cross-linking results in a material with a decreased crystallinity. Cross-linking is accomplished by irradiation in a molten state or photo cross-linking in a molten state, or cross-linking with a free radical generating chemical, and annealing the cross-linked polymer to pre-shrink it. Residuals from the chemical cross-linking reaction, however, are a regulatory concern and may contribute to long-term oxidative degradation.
It remains an object of the present invention, therefore, to provide a process for treating UHMWPE for use in orthopaedic implants such that the long-term wear properties of the UHMWPE are improved.
It is another object of the present invention to provide a process for treating UHMWPE for use in orthopaedic implants in vivo such that the performance of the implants in situ is improved.
It is well known in the published clinical literature that fine (micrometer and sub-micrometer sized) wear debris produced from bearing articulation of orthopaedic implants can elicit a macrophage cell-mediated response in the host body, which eventually leads to aseptic loosening of the implants and need for revision surgery. In general, bearing couples are formed from a combination of a soft material-ultra high molecular weight polyethylene (UHMWPE)-articulating against a hard material-metal or ceramic. It is the soft UHMWPE material which suffers the predominant wear in this soft-on-hard wear couple. Improvements in the wear resistance of UHMWPE, therefore, are expected to reduce the generation of fine particulate debris during articulation.
Although related art explicitly acknowledges the role particulate wear debris in the cell-mediated cascade which ultimately leads to aseptic loosening and revision surgery, it only anticipates a one-to-one relationship between improvements in gravimetric wear resistance and reduction in wear particulate debris numbers. The art explicitly or implicitly assumes a reduction in gravimetric wear will result in a concomitant reduction in the generation of wear particles. The teachings of the art do not necessarily result in the desired reductions in the generation of wear particles.
The prior art teaches that increased crosslinking energy corresponds to a decreased gravimetric wear. It presumes that this corresponds to a decrease in the number of wear particles. It also presumes that this corresponds to a decrease in the biological reaction to the wear debris produced, which may be false. The inventors of the present invention have found that decreased gravimetric wear does not necessarily correlate with decreased particle number and therefore may not correlate to decreased biological reaction. The present invention illustrates that there is not a continuum between crosslinking energy dose and the generation of wear particles.
The uniqueness of this work is that when crosslinking medical grade UHMWPE with gamma irradiation, the art is inadequate in predicting a relationship between the absorbed radiation dose and generation of wear debris in hip simulator testing. Within the range of acceptable dose, ranging from 5 MRad (significant reduction in gravimetric wear) to 15 MRad (acceptable upper limit for material strength considerations), the 10 MRad dose has been shown to fulfill the requirement for reduced wear debris generation. Alternative sources of irradiation (e.g., electron beam), or other gamma radiation doses between 5 and 15 MRad are predicted to also reduce the generation of particulate debris.
Recently, Green et al. (Green et al., 2000) found that smaller UHMWPE particles (0.24 xcexcm) produced bone resorbing activity in vitro at a lower volumetric dose than larger particles (0.45 xcexcm and 1.71 xcexcm). This evidence suggests that finer wear particles may elicit a greater macrophage response than larger particles. Thus, finer wear debris generated at orthopaedic bearing couples should be fully characterized to accurately predict macrophage response. This is particularly important for new bearing materials, such as crosslinked UHMWPE, which have been reported by Bhambri et al. (Bhambri et al., 1999) to generate smaller wear particles (mean diameter of less than 0.1 xcexcm) than conventional UHMWPE liners when tested in a hip simulator.
Because the cellular response to wear debris has been found to be dependent upon particle number and size, among other factors, the introduction of a new orthopaedic bearing material should be supported by an accurate description of wear particle parameters. The present invention teaches that filter membranes with very fine pore sizes (at most 0.05 xcexcm) should be used to isolate UHMWPE wear debris from joint simulator serum and periprosthetic tissue to ensure an accurate description of particle characteristics.
Prior to the present invention, there was not an accurate way to predict the number and size of wear particles of UHMWPE. There was an assumption in the art the increasing radiation caused decreased wear resistance. The methods used in the art use filters with too large of a pore size and, consequently, many of the smaller particles pass through the filter and are not detected. A large number of the particles created by wear of UHMWPE were being missed by the previous detection method.
Therefore, it is an objective of the present invention to provide methods and medical implants related to the prevention and decrease of osteolysis produced by wear of the ultrahigh molecular weight polyethylene (UHMWPE).
An embodiment of the present invention is a method for isolating wear particles from an ultrahigh molecular weight polyethylene (UHMWPE) medical implant for use in the body comprising the steps of: crosslinking the UHMWPE; annealing the UHMWPE; machining UHMWPE to form an implant; wear testing the implant; harvesting wear particles; and filtering the particles using 0.05 xcexcm or smaller pore size filters. The machining may be performed before crosslinking. The crosslinking may be performed using electromagnetic radiation or energetic subatomic particles. The crosslinking may be performed using gamma radiation, e-beam radiation, or x-ray radiation. In another aspect of the invention, the crosslinking may be performed using chemical crosslinking. The crosslinking may be at a dose of greater than five but less than or equal to fifteen MegaRad (MRad) or at a dose of greater than five but less than or equal to ten MegaRad (MRad). Annealing may be performed in the melt stage. In a further aspect of the invention, the annealing may be performed in an inert or ambient environment. The annealing may be performed below or equal to 150xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing is performed below about 150xc2x0 C. and above about 140xc2x0 C. and the crosslinking is sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect, the annealing may be performed at 147xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing may be performed at 140xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. Wear testing may occur on a joint simulator. The joint simulator may simulate the hip joint or knee joint of a human. The wear testing may occur in vivo. The harvesting may be performed using acid digestion, base digestion, or enzymatic digestion. The implant may have a polymeric structure with greater than about 300 angstrom lamellar thickness.
Another embodiment of the present invention is a method of preparing an UHMWPE medical implant for use in the body having a decreased wear particle number comprising the steps of: crosslinking the UHMWPE; annealing the UHMWPE; and machining UHMWPE to form an implant; wherein the wear particles that are decreased in number are greater than 0.125 xcexcm in diameter. The machining may be performed before crosslinking. The crosslinking may be performed using electromagnetic radiation or energetic subatomic particles. The crosslinking may be performed using gamma radiation, e-beam radiation, or x-ray radiation. In another aspect of the invention, the crosslinking may be performed using chemical crosslinking. The crosslinking may be at a dose of greater than five but less than or equal to fifteen MegaRad (MRad) or at a dose of greater than five but less than or equal to ten MegaRad (MRad). Annealing may be performed in the melt stage. In a further aspect of the invention, the annealing may be performed in an inert or ambient environment. The annealing may be performed below or equal to 150xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing is performed below about 150xc2x0 C. and above about 140xc2x0 C. and the crosslinking is sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect, the annealing may be performed at 147xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing may be performed at 140xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. Wear testing may occur on a joint simulator. The joint simulator may simulate the hip joint or knee joint of a human. The wear testing may occur in vivo. The harvesting may be performed using acid digestion, base digestion, or enzymatic digestion. The implant may have a polymeric structure with greater than about 300 angstrom lamellar thickness.
Yet another embodiment of the present invention is a method of decreasing macrophage response to an UHMWPE medical implant for use in the body comprising the steps of: performing wear particle analysis; and crosslinking the UHMWPE at a dose level exhibiting the lowest particle number per million cycles of the hip simulator wherein the number of particles present was determined using a 0.05 xcexcm or smaller pore size filter.
Still another embodiment of the present invention is a method of decreasing macrophage response to an UHMWPE medical implant in the body comprising crosslinking UHMWPE prior to implantation in a patient wherein the total volume of wear particles is decreased and the total number of wear particles is decreased. The crosslinking may be performed using electromagnetic radiation or energetic subatomic particles. In an aspect of the present invention, crosslinking may be performed using gamma radiation, e-beam radiation, or x-ray radiation or chemical crosslinking. In another aspect of the invention, the crosslinking may be at a dose of greater than five but less than or equal to fifteen MegaRad (MRad) or greater than five but less than or equal to ten MegaRad (MRad).
Another embodiment of the present invention is a method of decreasing macrophage response to an UHMWPE medical implant for use in the body comprising the steps of: crosslinking the UHMWPE; annealing the UHMWPE; machining UHMWPE to form an implant; wear testing the implant; harvesting wear particles; filtering the particles using 0.05 xcexcm or smaller pore size filters; characterizing the wear particles; determining the number of particulate debris; and selecting the crosslinking method for implants that gives the lowest number of particulate debris. The machining may be performed before crosslinking. The crosslinking may be performed using electromagnetic radiation or energetic subatomic particles. The crosslinking may be performed using gamma radiation, e-beam radiation, or x-ray radiation. In another aspect of the invention, the crosslinking may be performed using chemical crosslinking. The crosslinking may be at a dose of greater than five but less than or equal to fifteen MegaRad (MRad) or at a dose of greater than five but less than or equal to ten MegaRad (MRad). Annealing may be performed in the melt stage. In a further aspect of the invention, the annealing may be performed in an inert or ambient environment. The annealing may be performed below or equal to 150xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing is performed below about 150xc2x0 C. and above about 140xc2x0 C. and the crosslinking is sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect, the annealing may be performed at 147xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing may be performed at 140xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. Wear testing may occur on a joint simulator. The joint simulator may simulate the hip joint or knee joint of a human. The wear testing may occur in vivo. The harvesting may be performed using acid digestion, base digestion, or enzymatic digestion. The implant may have a polymeric structure with greater than about 300 angstrom lamellar thickness. In another embodiment of the invention, the characterization may be by a high resolution microscopic method or an automatic particle counter. In a further aspect of the present invention, the characterization may be by scanning electron microscopy or automatic particle counter.
Yet another embodiment of the present invention is a method of decreasing macrophage response to an UHMWPE medical implant for use in the body comprising the steps of: crosslinking the UHMWPE; annealing the UHMWPE; machining UHMWPE to form an implant; wear testing the implant; harvesting wear particles; filtering the particles using 0.05 xcexcm or smaller pore size filters; characterizing the wear particles; determining the number of particulate debris; determining the total particle surface area; and selecting the crosslinking method for implants that gives the lowest total particle surface area. Machining may be performed before said crosslinking.
Still another embodiment of the present invention is a method of decreasing osteolysis of an UHMWPE medical implant for use in the body comprising the steps of: crosslinking the UHMWPE; annealing the UHMWPE; machining UHMWPE to form an implant; wear testing the implant; harvesting wear particles; filtering the particles over 0.05 xcexcm or smaller pore size filters; characterizing the wear particles; determining the number of particulate debris; and selecting the crosslinking dose level to crosslink implants that exhibits the lowest number of particulate debris. The machining may be performed before crosslinking. The crosslinking may be performed using electromagnetic radiation or energetic subatomic particles. The crosslinking may be performed using gamma radiation, e-beam radiation, or x-ray radiation. In another aspect of the invention, the crosslinking may be performed using chemical crosslinking. The crosslinking may be at a dose of greater than five but less than or equal to fifteen MegaRad (MRad) or at a dose of greater than five but less than or equal to ten MegaRad (MRad). Annealing may be performed in the melt stage. In a further aspect of the invention, the annealing may be performed in an inert or ambient environment. The annealing may be performed below or equal to 150xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing is performed below about 150xc2x0 C. and above about 140xc2x0 C. and the crosslinking is sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect, the annealing may be performed at 147xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing may be performed at 140xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. Wear testing may occur on a joint simulator. The joint simulator may simulate the hip joint or knee joint of a human. The wear testing may occur in vivo. The harvesting may be performed using acid digestion, base digestion, or enzymatic digestion. The implant may have a polymeric structure with greater than about 300 angstrom lamellar thickness. In another embodiment of the invention, the characterization may be by a high resolution microscopic method or an automatic particle counter. In a further aspect of the present invention, the characterization may be by scanning electron microscopy or automatic particle counter.
Another embodiment of the present invention is a method of decreasing osteolysis of an UHMWPE medical implant for use in the body comprising the steps of: crosslinking the UHMWPE; annealing the UHMWPE; machining UHMWPE to form an implant; wear testing he implant; harvesting wear particles; filtering the particles using 0.05 xcexcm or smaller pore size filters; characterizing the wear particles; determining the number of particulate debris; determining the total particle surface area; and selecting the crosslinking method for implants that gives the lowest total particle surface area. Machining is performed before said crosslinking.
Yet another embodiment of the present invention is a method of decreasing macrophage response to a UHMWPE medical implant for use in the body comprising the steps of crosslinking the UHMWPE, simulating use in a host, and testing serum for particulate debris using a 0.05 xcexcm pore size filter, wherein particles of the diameter of 0.1 xcexcm to 1 xcexcm cause increased macrophage response. The machining may be performed before crosslinking. The crosslinking may be performed using electromagnetic radiation or energetic subatomic particles. The crosslinking may be performed using gamma radiation, e-beam radiation, or x-ray radiation. In another aspect of the invention, the crosslinking may be performed using chemical crosslinking. The crosslinking may be at a dose of greater than five but less than or equal to fifteen MegaRad (MRad) or at a dose of greater than five but less than or equal to ten MegaRad (MRad). Wear testing may occur on a joint simulator. The joint simulator may simulate the hip joint or knee joint of a human.
Still another embodiment of the present invention is a cross-linked UHMWPE medical implant for use in the body that exhibits decreased osteolysis (or macrophage response) in comparison to conventional treatment of UHMWPE due to a particle number of less than 5xc3x971012 per year upon testing for wear resistance.
Another embodiment of the present invention is an UHMWPE medical implant for use in the body having a decreased wear particle number of particles created by the steps comprising of: crosslinking the UHMWPE; annealing the UHMWPE; machining UHMWPE to form an implant; wear testing the implant; harvesting wear particles; filtering the particles over 0.05xcexcm or smaller pore size filters; characterizing the wear particles; determining the number of particulate debris; and selecting the crosslinking method to crosslink implants that exhibits the lowest number of particulate debris; wherein the wear particles that are decreased in number are greater than 0.125 xcexcm in diameter. The machining may be performed before crosslinking. The crosslinking may be performed using electromagnetic radiation or energetic subatomic particles. The crosslinking may be performed using gamma radiation, e-beam radiation, or x-ray radiation. In another aspect of the invention, the crosslinking may be performed using chemical crosslinking. The crosslinking may be at a dose of greater than five but less than or equal to fifteen MegaRad (MRad) or at a dose of greater than five but less than or equal to ten MegaRad (MRad). Annealing may be performed in the melt stage. In a further aspect of the invention, the annealing may be performed in an inert or ambient environment. The annealing may be performed below or equal to 150xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing is performed below about 150xc2x0 C. and above about 140xc2x0 C. and the crosslinking is sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect, the annealing may be performed at 147xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. In another aspect of the present invention, the annealing may be performed at 140xc2x0 C. The crosslinking may be sufficient to form an implant with a trans-vinylene index of greater than or equal to 0.10 or greater than about 0.15 and less than about 0.20. Wear testing may occur on a joint simulator. The joint simulator may simulate the hip joint or knee joint of a human. The wear testing may occur in vivo. The harvesting may be performed using acid digestion, base digestion, or enzymatic digestion. The implant may have a polymeric structure with greater than about 300 angstrom lamellar thickness. In another aspect of the invention, the characterization may be by a high resolution microscopic method or an automatic particle counter. In a further aspect of the present invention, the characterization may be by scanning electron microscopy or automatic particle counter.
As used herein the specification, xe2x80x9caxe2x80x9d or xe2x80x9canxe2x80x9d may mean one or more. As used herein in the claim(s), when used in conjunction with the word xe2x80x9ccomprisingxe2x80x9d, the words xe2x80x9caxe2x80x9d or xe2x80x9canxe2x80x9d may mean one or more than one. As used herein xe2x80x9canotherxe2x80x9d may mean at least a second or more.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.